We propose to conduct a series of clinical trials designed to evaluate the effectiveness of innovative versus standard treatments for opioid and cocaine abusers. These studies will be aimed at three groups of drug abusing patients who have been shown to be at particularly high risk for treatment failure: a. dually diagnosed (opioid dependence plus other psychopathology) opioid addicts on methadone maintenance, b. cocaine abusers who are concurrently abusing alcohol, and c. opioid addicts undergoing outpatient detoxification. All trials will utilize experimental designs with the following features: random assignment, outcome assessment by blind evaluators, use of placebo controls in pharmacotherapies, use of treatment manuals for psychotherapies, use of a comprehensive battery of reliable and validated assessments, monitoring the process of treatment delivery, and extended follow-up assessments. Across all studies, targeted outcomes include reduction of illicit substance use, program compliance and retention, improved psychosocial functioning, and outcomes specifically related to the type of treatment received. Programmatically, these clinical trials will increase the number of patients treated because experimental treatments will be provided free of charge and subjects will be assigned to special treatment slots created for this project. The following studies are proposed: 1. A randomized clinical trial evaluating the efficacy of fluoxetine versus placebo as treatment of methadone maintained opioid addicts who are either depressed or facing administrative discharge because of continued illicit drug use. 2. A randomized clinical trial which will focus on detection of patienttreatment matching effects and evaluate the efficacy of three ambulatory treatment approaches for concurrent abusers of cocaine and alcohol: a. 12-step oriented individual therapy, b. Cognitive-behavioral coping skills training and c.Motivational enhancement therapy. 3: A randomized clinical trial evaluating the comparative efficacy of three pharmacological approaches for ambulatory detoxification of opioid addicts: a.Clonidine alone, b. a combination of clonidine and naltrexone, and c. buprenorphine.